1. Field of the Invention
The present invention relates to an allergy prevention method or treatment method, diet and oral drug, and more particularly, to an allergy prevention method or treatment method, diet and oral drug that modify immune response different from that of transdermal/intravenous administration by oral administration.
2. Description of the Related Art
Transforming growth factor-β (TGF-β) is one of bioactive cytokines, identified during the 1980s, contained abundantly in human milk, and a multifunctional cytokine that regulates cell growth, survival and differentiation, which is disclosed in “Transforming growth factor-beta (TGF-β) in human milk”, Clin Exp Immunol Vol. 94(1):220-224, 1993 October.
TGF-β is considered an essential molecule in survival of living being, because the gene arrangement is conserved with excellence in fly, frog, mouse, human and the like, a TGF-β receptor exits in almost all the cells in the body, and mice with artificially lacked TGF-β (gene knockout mice) die during a fetal period.
From previous epidemiological studies, it is reported that an amount of TGF-β taken from human milk is inversely proportional to a rate of crisis of allergic diseases such as atopic dermatitis during infancy (see “TGF-β in human milk is associated with wheeze in infancy”, J Allergy Clin Immunol Vol. 112(4):723-728, 2003 October), and that the rate of crisis of allergic diseases of infants decreases when mothers take probiotics during pregnant and lactation, where the result is associated with the amount of TGF-β in human milk.
Further, for the purpose of prevention and treatment of diseases, studies of TGF-β transdermal/intravenous administration have been performed on various zoonoses mice. There are also examples that clinical tests are actually performed for the purpose of prevention and treatment of human diseases.
However, disease prevention/treatment effects of TGF-β transdermal/intravenous administration have not been determined, and there remain many issues to overcome by practical use as a drug, such as weakness of the action to diseases, systemic adverse reaction provoked by administration of TGF-β and the like.
Allergic diseases such as pollinosis, bronchial asthma, atopic dermatitis, allergic asthma and the like grow year after year, and are becoming a social issue.
In recent years, the food allergy has also surged mainly among infants. They develop eczema and/or hives by intake of an allergy causal substance contained in a diet, and in the serious case, may die by anaphylactic shock. Causal substances of the food allergy depend on individuals, but are usually familiar foods such as milk, egg, wheat, rice, buckwheat noodle, seafood and the like. It is difficult to manage to live while completely keeping away from the allergy causal substances in modern society.
The inventor of the present invention noted the report (see “TGF-β in human milk is associated with wheeze in infancy”, J Allergy Clin Immunol Vol. 112(4):723-728, 2003 October) that the intake of TGF-β from human milk is inversely proportional to the number of crises of asthma of infants, and proceeded with empirical researches to prevent and/or treat food allergic diseases by oral administration of TGF-β.
It has conventionally been considered that orally taken protein molecules are decomposed in gastrointestine and do not exert the action systemically, and sufficient verification has not been performed also on TGF-β. The inventor of the invention found that as a result of verification of effects of TGF-β oral administration on the immune system using model animals, when high-dose TGF-β is orally administered, TGF-β is not decomposed, and modifies immune response in a manner specific to oral administration different from that in conventional transdermal/intravenous administration.
In the case of conventional transdermal/intravenous administration, while Th2 immune response (production of IgE antibody and the like) involved in the allergy reaction is suppressed, Th1 immune response to the cancer and infection (cell immunity such as the defense reaction to cancer cells and pathogens) is also suppressed. The immune response is thus totally suppressed by administration of TGF-β, and there is the risk of immune deficiency.
The inventor verified the effects exerted on the systemic immune system by orally administering TGF-β to food allergy model mice. In the stage prior to verification, it was expected that TGF-β, protein molecule, is decomposed in gastrointestine, and does not exhibit the immune suppression effect as in transdermal/intravenous administration. However, actually, orally administered TGF-β selectively suppressed only Th2 immune response involved in the allergic reaction, while enhancing Th1 immune response to the cancer and infection, and thus exhibited the immune suppression effect different from that in transdermal/intravenous administration. Therefore, the inventor found that TGF-β is a protein molecule, but when orally administered, is not decomposed in gastrointestine, and that orally administered TGF-β modifies specific immune response, and reached completion of the invention.